_:b430238664 . _:b430238745 . . _:b430238716 . _:b430238667 . . _:b430238666 . _:b430238545 . _:b430238677 . _:b430238756 . _:b430238533 . _:b430238676 . . _:b430238667 . _:b430238502 . _:b430238477 . _:b430238679 . _:b430238678 . _:b430238673 . _:b430238676 . _:b430238861 . _:b430238672 . . _:b430238675 . _:b430238878 . _:b430238674 . . _:b430238531 . . . _:b430238685 . _:b430238599 . _:b430238684 . . _:b7458011 "discussion" . . _:b430238617 . _:b430238687 . _:b430238917 . _:b430238803 . _:b430238592 . _:b430238686 . _:b430238899 . . _:b430238817 . _:b430238635 . _:b430238681 . . . _:b7458022 . _:b430238680 . _:b430238846 . _:b430238720 . . _:b7457985 . _:b430238683 . _:b7457989 . _:b430238522 . . _:b430238682 . _:b7458016 . _:b430238813 . _:b430238693 . _:b430238692 . _:b430238670 . . _:b430238837 . _:b430238785 . _:b430238695 . . _:b430238694 . . . _:b430238689 . . . . . _:b430238688 . _:b430238464 . . _:b430238691 . _:b430238690 . _:b430238701 . . _:b430238824 . _:b430238700 . . _:b7458002 . _:b430238703 . _:b7458014 . _:b430238702 . _:b430238722 . _:b430238589 . . _:b430238797 . _:b7458011 . _:b430238697 . _:b430238768 . _:b430238696 . _:b430238530 . _:b430238699 . _:b7458010 . _:b7457996 . . _:b430238896 . _:b430238698 . . _:b430238844 . _:b430238709 . _:b430238634 . . _:b430238585 . _:b430238481 . _:b430238708 . _:b430238869 . _:b430238711 . . _:b430238710 . _:b7458007 "The prediction of TAP transport efficiency is based on the matrix method described in Peters et al. (>>2003<<). The method predicts TAP transport efficiency of peptides by a scoring method using only the C terminus and the tree N-terminal residues of a peptide." . _:b430238793 . _:b430238478 . _:b430238705 . . . _:b7457961 . _:b430238704 . _:b430238550 . _:b430238513 . _:b430238524 . _:b430238707 . . _:b430238706 . _:b430238911 . _:b7457960 . . . . _:b7457974 . . _:b430238717 . _:b430238770 . _:b7458000 "Next, we compared the performance of the NetCTLpan method to the MHC-pathway method (Tenzer et al. >>2005<<). This method has earlier been shown to be a state-of-the-art MHC class I pathway predictor (Larsen et al. 2005)." . _:b430238687 . _:b430238716 . . _:b430238719 . _:b7457987 "The predictive performance of the NetCTLpan method is validated on large and MHC diverse data sets derived from the SYFPEITHI (Rammensee et al. >>1999<<) and Los Alamos HIV databases (http://www.hiv.lanl.gov/), and its performance has been compared to other state-of-the-art CTL epitope prediction methods." . . _:b430238718 . _:b430238505 . . _:b430238713 . _:b430238821 . _:b430238913 . . _:b430238712 . _:b430238820 . . . . _:b430238715 . . . _:b430238714 . _:b430238744 . . . _:b430238719 . _:b430238494 . _:b430238619 . _:b7457982 "Several other groups have developed methods for CTL epitope identification by integrating steps of the MHC class I pathway (MAPPP, Hakenberg et al. 2003; WAPP, D\u00F6nnes and Kohlbacher 2005); EpiJen, Doytchinova et al. >>2006<<; MHC-pathway, Tenzer et al. 2005)." . _:b430238783 . . _:b430238867 . _:b430238800 . _:b7457972 . _:b430238632 . _:b430238835 . . _:b430238708 . . . . . _:b430238557 . _:b430238457 . . _:b430238786 . _:b430238901 . . _:b430238606 . . . _:b430238746 . _:b430238673 . _:b430238792 . . _:b430238841 . _:b430238763 . . . . . . . _:b430238849 . _:b430238915 . . _:b7458020 . . . . _:b430238856 . _:b430238862 . _:b7457976 "We have previously described a method, NetCTL (Larsen et al. 2007, >>2005<<), integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions to an overall prediction of CTL epitopes." . _:b430238638 . _:b7457985 "In contrast to this, the NetCTL method has not been updated since 2007, and the MHC binding prediction remains limited to the 12 common HLA supertypes (Lund et al. >>2004<<). In the following, we describe an improved and extended version of NetCTL, called NetCTLpan, which is able to make predictions for all MHC class I molecules with known protein sequence. In addition, NetCTLpan can identify 8-, 9-, 10-," . . . . _:b430238654 . _:b430238905 . _:b7458009 "NetChop C-term 3.0 (Nielsen et al. >>2005<<) was used for predicting cleavage sites. As in the original NetCTL publication, only the C-terminal cleavage score of a peptide was included." . . . _:b430238805 . . _:b7457986 . . . _:b7457987 . . . . . _:b7457991 "It has been suggested that supertype-specific differences exist in how dependent MHC class I presentation of peptides is on transport via TAP molecules (Brusic et al. 1999; Anderson et al. 1993; Henderson et al. 1992; Smith and Lutz >>1996<<) and proteasomal cleavage (Wherry et al. 2006)." . _:b430238919 . _:b430238574 . _:b7457994 . _:b7457992 . . _:b7458010 "Finally, it is becoming apparent that not all MHC molecules present peptides at the same binding threshold (Rao et al. >>2009<<). This observation would make an evaluation, where data for different HLA alleles is pooled, highly problematic, as illustrated in Fig.\u00A01. Here, a ROC curve is shown for a pooled set of 29 HLA-A*0101, 50 HLA-B*4402, and 31 HLA-B*5101" . _:b430238529 . . "10.1007%2Fs00251-010-0441-4" . . _:b430238880 . . _:b7458018 "Data used for training the individual MHC class I pathway predictors\u2014MHC binding (Nielsen et al. 2007; Hoof et al. 2009), proteasomal cleavage (Nielsen et al. >>2005<<), and TAP transport efficiency (Peters et al. 2003)\u2014was removed from the data set, downsizing it to 2,309 unique HLA class I ligand pairs." . . . . _:b430238738 . . _:b430238558 . _:b430238643 . _:b430238549 . . . _:b7457974 "The most restricting step in antigen presentation is peptide binding to MHC class I molecule (Yewdell and Bennink >>1999<<)." . _:b430238904 . . _:b7457984 . _:b430238607 . _:b7457978 . . . _:b430238541 . _:b430238491 . _:b430238693 . _:b430238602 . _:b430238566 . _:b430238614 . _:b430238751 . . _:b430238586 . _:b430238757 . . . . . _:b430238852 . _:b430238718 . _:b430238795 . _:b7458015 . _:b7457996 "results" . _:b430238517 . _:b7457997 "It has been suggested that such a rescaling might remove genuine biological differences between MHC molecules and potentially lowers the epitopes predictive performance (MacNamara et al. >>2009<<). To investigate, if the predictive performance of the NetCTLpan method is influenced when including rescaling, we defined a rescaling factor for each MHC allele and used that factor to rescale all MHC binding affinity values before" . . _:b430238907 . . _:b430238483 . _:b430238663 . _:b7458008 "The matrix published in Peters et al. (>>2003<<) was modified as all values in the TAP scoring matrix were multiplied by a factor of \u22121, in order to have a high predicted value corresponding to high transport efficiency." . . . . . . . _:b430238661 . _:b430238864 . _:b430238519 . _:b7457963 "One of the first steps involved in MHC class I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. >>1999<<; Craiu et al. 1997; Altuvia and Margalit 2000; Mo et al. 1999; Stoltze et al. 1998; Juncker et al. 2009)." . _:b430238903 . _:b430238743 . . . _:b7458024 . . _:b430238730 . _:b430238492 . . _:b430238885 . . _:b430238918 . _:b430238467 . _:b430238692 . _:b7457967 "is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al. 1997; Altuvia and Margalit 2000; Mo et al. 1999; Stoltze et al. >>1998<<; Juncker et al. 2009). These peptides may be trimmed at the N-terminal end by cytosolic exopeptidases (L\u00E9vy et al. 2002)." . . . _:b430238736 . . . . _:b430238727 . . _:b430238590 . . . . . _:b430238651 . _:b430238895 . . _:b430238897 . . . . . _:b430238523 . . . _:b430238497 . . _:b430238448 . . _:b430238826 . . . _:b430238559 . _:b430238725 . _:b430238843 . _:b430238724 . . _:b430238468 . _:b430238727 . . _:b430238703 . . _:b430238726 . _:b430238721 . _:b430238749 . . _:b430238720 . _:b430238831 . . _:b430238610 . . _:b430238723 . _:b430238914 . . _:b430238759 . _:b430238722 . . . . _:b7457980 "Several other groups have developed methods for CTL epitope identification by integrating steps of the MHC class I pathway (MAPPP, Hakenberg et al. >>2003<<; WAPP, D\u00F6nnes and Kohlbacher 2005); EpiJen, Doytchinova et al. 2006; MHC-pathway, Tenzer et al. 2005)." . . _:b430238733 . _:b430238678 . . _:b430238732 . _:b430238526 . _:b430238725 "2"^^ . . _:b430238735 . . _:b430238724 "2"^^ . _:b430238734 . _:b7458001 "This method has earlier been shown to be a state-of-the-art MHC class I pathway predictor (Larsen et al. >>2005<<). Like the NetCTLpan method, this method integrates predictions of MHC binding, C-terminal proteasomal cleavage, and TAP transport into a combined pathway presentation score. Here, we use the method with default parameters via the link" . _:b430238699 . _:b430238727 "2"^^ . _:b430238729 . . _:b430238726 "2"^^ . _:b430238728 . _:b430238721 "2"^^ . _:b430238731 . _:b430238834 . _:b430238720 "2"^^ . _:b430238730 . _:b430238723 "2"^^ . _:b430238881 . _:b430238741 . _:b430238722 "2"^^ . _:b430238740 . _:b430238733 "2"^^ . . _:b430238743 . . _:b430238732 "2"^^ . . _:b430238514 . _:b430238742 . _:b430238735 "2"^^ . _:b430238737 . . _:b430238909 . _:b430238734 "2"^^ . _:b430238736 . _:b430238729 "2"^^ . _:b430238739 . _:b430238728 "2"^^ . . _:b430238738 . _:b430238731 "2"^^ . _:b430238782 . _:b430238749 . _:b7457983 "groups have developed methods for CTL epitope identification by integrating steps of the MHC class I pathway (MAPPP, Hakenberg et al. 2003; WAPP, D\u00F6nnes and Kohlbacher 2005); EpiJen, Doytchinova et al. 2006; MHC-pathway, Tenzer et al. >>2005<<). All these methods are limited by the fact that they only allow for prediction of peptide binding to a highly limited set of different MHC molecules." . _:b430238601 . _:b430238730 "2"^^ . . _:b430238748 . . _:b430238666 . _:b430238741 "2"^^ . . _:b430238925 . _:b430238751 . _:b430238682 . _:b430238595 . _:b430238740 "2"^^ . _:b430238750 . _:b430238597 . . . _:b430238743 "2"^^ . _:b430238745 . _:b430238742 "2"^^ . _:b430238744 . _:b430238737 "2"^^ . _:b430238747 . _:b430238736 "2"^^ . _:b430238648 . _:b430238746 . _:b430238739 "2"^^ . _:b430238613 . _:b430238757 . . _:b430238738 "2"^^ . _:b430238756 . _:b430238749 "2"^^ . _:b430238759 . _:b430238920 . . _:b430238877 . _:b430238568 . _:b430238748 "2"^^ . . _:b430238758 . _:b430238884 . _:b430238819 . _:b430238751 "2"^^ . _:b430238753 . . _:b430238750 "2"^^ . _:b430238735 . _:b7457986 "The method has been trained on a large data set of experimentally identified MHC ligands from the SYPFEITHI database (Rammensee et al. >>1999<<)." . _:b430238752 . _:b7457979 . _:b430238496 . _:b430238745 "2"^^ . _:b430238755 . _:b430238889 . _:b430238450 . _:b7457981 "Several other groups have developed methods for CTL epitope identification by integrating steps of the MHC class I pathway (MAPPP, Hakenberg et al. 2003; WAPP, D\u00F6nnes and Kohlbacher >>2005<<); EpiJen, Doytchinova et al. 2006; MHC-pathway, Tenzer et al. 2005)." . _:b430238511 . _:b430238744 "2"^^ . _:b430238754 . _:b7458019 . . _:b430238747 "2"^^ . . _:b430238765 . _:b430238583 . . _:b430238746 "2"^^ . . _:b430238764 . _:b430238757 "2"^^ . _:b430238767 . _:b430238893 . . _:b430238756 "2"^^ . . _:b430238766 . . _:b430238759 "2"^^ . _:b430238908 . _:b430238761 . _:b430238866 . _:b430238822 . _:b430238758 "2"^^ . _:b430238581 . _:b430238760 . _:b430238705 . _:b430238753 "2"^^ . _:b430238543 . _:b430238763 . _:b430238752 "2"^^ . _:b430238762 . _:b430238775 . _:b430238755 "2"^^ . _:b430238482 . _:b430238906 . _:b430238773 . _:b430238754 "2"^^ . _:b430238772 . _:b430238765 "2"^^ . _:b430238775 . _:b430238798 . _:b430238764 "2"^^ . _:b430238774 . _:b430238615 . . _:b430238767 "2"^^ . _:b430238769 . _:b430238923 . . _:b430238766 "2"^^ . . _:b430238768 . _:b430238761 "2"^^ . . _:b430238771 . _:b430238809 . _:b430238760 "2"^^ . _:b430238770 . . _:b430238763 "2"^^ . _:b430238781 . _:b430238762 "2"^^ . _:b430238780 . _:b430238818 . _:b430238811 . _:b430238773 "2"^^ . _:b430238783 . _:b430238772 "2"^^ . _:b430238782 . . _:b7457990 "It has been suggested that supertype-specific differences exist in how dependent MHC class I presentation of peptides is on transport via TAP molecules (Brusic et al. 1999; Anderson et al. 1993; Henderson et al. >>1992<<; Smith and Lutz 1996) and proteasomal cleavage (Wherry et al. 2006)." . . _:b430238775 "2"^^ . . _:b430238777 . . _:b430238801 . _:b430238528 . . _:b430238774 "2"^^ . _:b430238776 . . _:b430238807 . . _:b430238769 "2"^^ . _:b430238779 . . _:b430238768 "2"^^ . _:b430238778 . _:b430238771 "2"^^ . _:b430238789 . _:b430238770 "2"^^ . _:b430238474 . _:b430238788 . _:b430238781 "2"^^ . . _:b430238791 . . . _:b430238780 "2"^^ . . _:b430238790 . _:b430238695 . _:b430238783 "2"^^ . _:b430238785 . _:b430238782 "2"^^ . _:b430238784 . _:b430238777 "2"^^ . _:b430238787 . _:b430238501 . . _:b430238776 "2"^^ . _:b430238724 . _:b430238786 . . _:b430238779 "2"^^ . . _:b430238797 . _:b430238702 . _:b430238778 "2"^^ . _:b430238796 . _:b430238830 . . _:b430238847 . _:b430238504 . _:b430238789 "2"^^ . _:b430238799 . _:b430238799 . _:b430238569 . _:b430238788 "2"^^ . . _:b430238798 . . . . _:b430238791 "2"^^ . _:b430238793 . . _:b430238456 . _:b430238790 "2"^^ . _:b430238792 . _:b430238814 . . _:b430238785 "2"^^ . _:b7457972 "of the peptides is transported by transporter associated with antigen processing (TAP) complex into the endoplasmatic reticulum (ER), where further N-terminal trimming occurs (Ritz and Seliger 2001; Koch et al. 2004; van Endert et al. >>1994<<; Schatz et al. 2008). Inside the ER, a peptide may bind to an MHC class I molecule and the peptide\u2013MHC complex will be transported to the cell surface, where it subsequently may be recognized by CTLs." . _:b430238452 . _:b430238795 . . _:b430238784 "2"^^ . _:b430238794 . _:b430238787 "2"^^ . . _:b430238805 . . _:b430238786 "2"^^ . _:b430238580 . _:b430238804 . _:b430238797 "2"^^ . _:b430238807 . _:b430238471 . . . _:b430238796 "2"^^ . _:b430238575 . _:b430238806 . . . _:b430238799 "2"^^ . _:b430238801 . _:b430238798 "2"^^ . _:b430238800 . _:b430238793 "2"^^ . . _:b430238803 . _:b430238576 . . _:b430238792 "2"^^ . _:b430238802 . _:b430238548 . . _:b430238795 "2"^^ . . . _:b430238813 . . . _:b430238561 . _:b430238794 "2"^^ . _:b430238812 . _:b430238473 . _:b430238805 "2"^^ . _:b430238815 . _:b430238872 . _:b430238804 "2"^^ . _:b430238814 . _:b7458007 . _:b430238652 . _:b430238807 "2"^^ . _:b7458017 "Data used for training the individual MHC class I pathway predictors\u2014MHC binding (Nielsen et al. 2007; Hoof et al. >>2009<<), proteasomal cleavage (Nielsen et al. 2005), and TAP transport efficiency (Peters et al. 2003)\u2014was removed from the data set, downsizing it to 2,309 unique HLA class I ligand pairs." . _:b430238809 . . _:b430238554 . _:b430238781 . _:b430238806 "2"^^ . _:b430238808 . . _:b430238801 "2"^^ . _:b430238811 . . _:b430238800 "2"^^ . . _:b430238810 . _:b7457964 . _:b7458003 "The current version of the pan-specific MHC class I binding prediction method, NetMHCpan-2.2 (Hoof et al. >>2009<<), is an updated version of the original NetMHCpan method (Nielsen et al. 2007)." . _:b430238803 "2"^^ . _:b430238821 . _:b7457965 . . _:b430238802 "2"^^ . _:b430238820 . . _:b7457966 . _:b430238791 . _:b430238813 "2"^^ . _:b430238823 . _:b7458008 . _:b7457967 . _:b430238630 . _:b430238812 "2"^^ . _:b430238570 . _:b430238822 . _:b7457960 . _:b430238815 "2"^^ . _:b430238817 . _:b430238498 . _:b7457961 . _:b430238814 "2"^^ . . _:b430238816 . _:b7457962 . . . _:b430238809 "2"^^ . _:b430238819 . _:b7457963 . . _:b430238808 "2"^^ . _:b7457964 "One of the first steps involved in MHC class I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al. >>1997<<; Altuvia and Margalit 2000; Mo et al. 1999; Stoltze et al. 1998; Juncker et al. 2009)." . . _:b430238818 . _:b430238645 . _:b7457972 . _:b430238537 . _:b430238764 . _:b430238811 "2"^^ . _:b430238829 . _:b7457973 . . _:b430238810 "2"^^ . _:b430238828 . . _:b7457974 . _:b430238821 "2"^^ . _:b430238831 . _:b7457975 . _:b430238820 "2"^^ . _:b430238830 . _:b7457979 "The NetCTL method has proven successful in identification of CTL epitopes from, for instance influenza (Wang et al. 2007), HIV (P\u00E9rez et al. 2008), and Orthopoxvirus (Tang et al. >>2008<<). Several other groups have developed methods for CTL epitope identification by integrating steps of the MHC class I pathway (MAPPP, Hakenberg et al. 2003; WAPP, D\u00F6nnes and Kohlbacher 2005); EpiJen, Doytchinova et al. 2006; MHC-pathway," . _:b7457968 . _:b430238823 "2"^^ . _:b430238825 . _:b7457969 . _:b430238710 . _:b430238822 "2"^^ . _:b430238854 . _:b430238824 . _:b7457970 . _:b430238817 "2"^^ . _:b430238827 . . _:b7457971 . _:b430238816 "2"^^ . _:b430238873 . _:b430238826 . _:b7457980 . _:b7457991 . _:b430238534 . _:b430238819 "2"^^ . _:b430238837 . _:b7457981 . _:b430238546 . _:b430238818 "2"^^ . _:b430238836 . _:b7457960 _:b7457988 . _:b7457982 . _:b430238662 . _:b7457960 _:b7457989 . _:b7458015 "The SYFPEITHI database (Rammensee et al. >>1999<<) was used as the source of MHC class I ligands. MHC class I binding peptides classified as ligands were downloaded in August 2009." . _:b430238631 . _:b430238573 . . _:b430238829 "2"^^ . _:b7457960 _:b7457990 . . _:b430238839 . _:b7457960 _:b7457991 . . _:b7457960 "introduction" . _:b7457960 _:b7457984 . _:b7457983 . . _:b7457960 _:b7457985 . _:b7457960 _:b7457986 . _:b430238828 "2"^^ . _:b7457960 _:b7457987 . _:b430238838 . . _:b7457976 . _:b430238831 "2"^^ . _:b430238833 . _:b7457960 _:b7457992 . _:b7457977 . _:b7457960 _:b7457993 . _:b7457960 _:b7457994 . _:b430238830 "2"^^ . _:b7457960 _:b7457995 . _:b430238832 . . _:b7457978 . _:b430238825 "2"^^ . _:b430238835 . _:b7457979 . . . _:b430238824 "2"^^ . _:b430238834 . _:b7457988 . . _:b430238827 "2"^^ . . _:b430238845 . _:b7457989 . _:b430238826 "2"^^ . _:b430238844 . _:b7457990 . _:b430238837 "2"^^ . _:b430238465 . _:b430238847 . _:b7457991 . . _:b430238731 . _:b430238836 "2"^^ . _:b430238846 . _:b430238921 . _:b7457984 . _:b430238839 "2"^^ . _:b430238841 . _:b7457985 . _:b430238509 . _:b430238838 "2"^^ . _:b430238840 . _:b7457986 . _:b430238625 . _:b430238833 "2"^^ . _:b430238843 . . _:b7457987 . _:b430238832 "2"^^ . _:b430238842 . _:b7457996 . _:b430238835 "2"^^ . _:b7457988 . . _:b430238853 . _:b7457997 . . _:b430238834 "2"^^ . _:b430238852 . _:b430238445 . _:b7457998 . _:b430238508 . _:b430238845 "2"^^ . _:b430238598 . _:b430238855 . _:b430238444 . _:b7457999 . . _:b430238844 "2"^^ . _:b430238854 . _:b430238447 . _:b7457992 . _:b430238847 "2"^^ . . _:b430238849 . _:b430238446 . _:b7457993 . _:b7457961 "In fact, it is estimated that only one out of 2,000 potential peptides will be immunodominant (Yewdell and Bennink >>1999<<). One of the first steps involved in MHC class I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al." . . . _:b430238846 "2"^^ . _:b430238700 . _:b430238848 . _:b7457994 . . _:b430238694 . _:b430238841 "2"^^ . . _:b430238851 . _:b430238527 . _:b7457995 . . _:b430238696 . _:b430238840 "2"^^ . _:b430238850 . _:b430238443 . _:b7458004 . . . _:b7457968 . _:b430238843 "2"^^ . _:b430238861 . _:b430238442 . _:b7458005 . . _:b430238842 "2"^^ . _:b430238860 . _:b430238453 . _:b7458006 . . _:b430238853 "2"^^ . _:b430238656 . _:b430238863 . _:b430238452 . _:b7458007 . . _:b430238852 "2"^^ . . _:b430238862 . _:b430238612 . _:b430238442 "22"^^ . _:b430238455 . _:b7458000 . _:b7457960 _:b7457964 . _:b430238447 "11"^^ . . _:b7457960 _:b7457965 . _:b7457960 _:b7457966 . _:b430238855 "2"^^ . . _:b430238857 . _:b7457960 _:b7457967 . _:b430238454 . _:b7458001 . _:b430238446 "12"^^ . _:b430238912 . _:b430238853 . _:b7457960 _:b7457961 . _:b7457960 _:b7457962 . _:b430238854 "2"^^ . _:b7457960 _:b7457963 . _:b430238856 . _:b430238449 . _:b7457960 _:b7457972 . _:b430238443 "19"^^ . _:b7458002 . _:b7457960 _:b7457973 . _:b7457960 _:b7457974 . _:b430238849 "2"^^ . _:b7457960 _:b7457975 . _:b430238859 . _:b430238448 . _:b7458003 . _:b7457960 _:b7457968 . . _:b7457960 _:b7457969 . _:b7457960 _:b7457970 . _:b430238848 "2"^^ . _:b430238444 "14"^^ . _:b430238858 . _:b7457960 _:b7457971 . _:b430238451 . _:b7458012 . _:b7457960 _:b7457980 . . . _:b7457960 _:b7457981 . . . _:b430238851 "2"^^ . _:b7457960 _:b7457982 . _:b430238445 "14"^^ . _:b430238869 . _:b7457960 _:b7457983 . _:b430238450 . _:b7458013 . _:b7457960 _:b7457976 . _:b7457960 _:b7457977 . _:b7457960 _:b7457978 . _:b430238850 "2"^^ . _:b7457960 _:b7457979 . _:b430238868 . _:b430238461 . _:b7458014 . _:b430238861 "2"^^ . _:b430238644 . _:b430238871 . _:b430238460 . _:b7458015 . _:b7457996 _:b7458000 . _:b7457996 _:b7458001 . _:b430238860 "2"^^ . _:b430238455 "10"^^ . _:b430238870 . _:b430238463 . _:b7458008 . _:b7457977 "The NetCTL method has proven successful in identification of CTL epitopes from, for instance influenza (Wang et al. >>2007<<), HIV (P\u00E9rez et al. 2008), and Orthopoxvirus (Tang et al. 2008)." . _:b7457973 "by transporter associated with antigen processing (TAP) complex into the endoplasmatic reticulum (ER), where further N-terminal trimming occurs (Ritz and Seliger 2001; Koch et al. 2004; van Endert et al. 1994; Schatz et al. >>2008<<). Inside the ER, a peptide may bind to an MHC class I molecule and the peptide\u2013MHC complex will be transported to the cell surface, where it subsequently may be recognized by CTLs." . . _:b430238633 . _:b430238863 "2"^^ . _:b430238454 "10"^^ . _:b430238865 . _:b430238462 . _:b7458009 . _:b430238784 . _:b430238862 "2"^^ . _:b430238453 "10"^^ . _:b430238864 . _:b430238457 . _:b7458010 . _:b430238857 "2"^^ . _:b430238452 "10"^^ . _:b430238867 . _:b430238456 . . _:b7458011 . _:b430238856 "2"^^ . _:b430238451 "10"^^ . _:b430238866 . _:b430238742 . _:b430238459 . _:b7458020 . _:b430238455 . _:b7457996 _:b7457997 . _:b7457996 _:b7457998 . _:b430238859 "2"^^ . _:b430238450 "10"^^ . _:b430238877 . _:b7457996 _:b7457999 . _:b430238458 . _:b7458021 . _:b430238461 . _:b430238858 "2"^^ . _:b430238449 "10"^^ . _:b430238876 . _:b7458022 . _:b430238869 "2"^^ . _:b430238879 . _:b430238448 "11"^^ . _:b7458023 . . _:b430238868 "2"^^ . _:b430238453 . . _:b430238878 . . _:b7458016 . _:b430238462 "8"^^ . . _:b430238871 "2"^^ . _:b430238709 . _:b430238873 . . _:b7458017 . _:b430238547 . . _:b430238463 "8"^^ . _:b430238870 "2"^^ . _:b430238872 . _:b7458018 . _:b430238767 . . _:b430238865 "2"^^ . _:b430238460 "9"^^ . . _:b430238875 . _:b7458019 . . _:b430238461 "8"^^ . _:b430238864 "2"^^ . _:b430238874 . . _:b430238480 . . . _:b430238458 "9"^^ . _:b430238867 "2"^^ . _:b430238885 . _:b430238475 . _:b430238459 "9"^^ . _:b430238866 "2"^^ . . _:b430238884 . . _:b430238806 . _:b430238877 "2"^^ . _:b430238456 "10"^^ . _:b7457990 . _:b430238887 . _:b7458014 _:b7458015 . . _:b430238486 . _:b430238876 "2"^^ . _:b430238457 "9"^^ . _:b430238886 . _:b430238470 "7"^^ . _:b7458024 . . _:b430238879 "2"^^ . _:b430238734 . _:b430238881 . _:b430238471 "7"^^ . _:b430238878 "2"^^ . . _:b430238880 . . _:b430238468 "8"^^ . _:b430238778 . _:b430238873 "2"^^ . _:b430238883 . _:b430238469 "7"^^ . _:b7458011 _:b7458012 . _:b7458011 _:b7458013 . _:b430238872 "2"^^ . _:b430238882 . . _:b430238466 "8"^^ . _:b430238551 . _:b430238776 . _:b430238875 "2"^^ . . _:b430238893 . . _:b430238467 "8"^^ . _:b430238874 "2"^^ . . _:b430238892 . _:b430238464 "8"^^ . _:b430238885 "2"^^ . _:b430238895 . _:b430238465 "8"^^ . _:b430238884 "2"^^ . _:b430238478 "6"^^ . _:b430238894 . _:b430238500 . . _:b430238887 "2"^^ . _:b430238479 "6"^^ . _:b430238889 . _:b430238608 . _:b430238711 . . _:b430238886 "2"^^ . _:b430238888 . . _:b430238476 "7"^^ . . _:b430238881 "2"^^ . _:b430238891 . _:b7457965 . _:b430238477 "7"^^ . _:b7458002 _:b7458008 . _:b7458014 _:b7458024 . . _:b7458002 _:b7458009 . _:b7458002 _:b7458010 . _:b430238880 "2"^^ . _:b430238890 . _:b430238474 "7"^^ . _:b7458002 _:b7458004 . _:b7458014 _:b7458020 . _:b430238458 . _:b7458014 _:b7458021 . _:b430238876 . _:b7458002 _:b7458005 . _:b7458014 _:b7458022 . _:b430238883 "2"^^ . _:b430238829 . _:b7458002 _:b7458006 . _:b7458014 _:b7458023 . _:b430238901 . _:b7458002 _:b7458007 . _:b430238475 "7"^^ . _:b7458014 _:b7458016 . _:b7458014 _:b7458017 . _:b7458014 _:b7458018 . _:b430238882 "2"^^ . _:b7458014 _:b7458019 . _:b430238900 . _:b7458002 _:b7458003 . . _:b430238472 "7"^^ . . _:b430238893 "2"^^ . . _:b430238903 . _:b430238922 . _:b430238473 "7"^^ . _:b430238892 "2"^^ . _:b430238486 "6"^^ . _:b430238902 . _:b430238521 . _:b430238895 "2"^^ . _:b430238487 "6"^^ . _:b430238897 . . . _:b430238894 "2"^^ . . _:b430238484 "6"^^ . _:b430238896 . _:b430238624 . _:b430238889 "2"^^ . _:b430238485 "6"^^ . _:b430238899 . _:b430238726 . _:b430238888 "2"^^ . . _:b430238898 . _:b430238482 "6"^^ . _:b430238485 . _:b430238891 "2"^^ . . _:b430238483 "6"^^ . _:b430238909 . . . _:b430238890 "2"^^ . _:b430238842 . _:b430238480 "6"^^ . _:b430238908 . _:b430238623 . _:b430238762 . _:b430238901 "2"^^ . _:b430238481 "6"^^ . _:b430238911 . _:b7457976 . _:b430238900 "2"^^ . _:b430238536 . _:b430238910 . . . . _:b430238493 "5"^^ . _:b430238903 "2"^^ . _:b430238905 . _:b430238902 "2"^^ . _:b430238492 "6"^^ . _:b430238904 . . _:b430238495 "5"^^ . _:b430238897 "2"^^ . _:b430238622 . _:b430238907 . _:b430238587 . . _:b430238896 "2"^^ . _:b430238494 "5"^^ . _:b430238490 "6"^^ . _:b7458022 "Each of the HLA alleles in the SYF data set was assigned a supertype association using the distance measure described by Nielsen et al. (>>2007<<). In short, an HLA allele was associated to the most similar supertype defined in terms of the correlation coefficient between NetMHCpan prediction scores for 1,000,000 random natural 9-mer peptides for the HLA allele in question and any" . _:b430238906 . . _:b7458005 "It has been evaluated as the best pan-specific method in large benchmark study (Zhang et al. >>2009<< and is now including the extension to perform predictions for 8-, 10-, and 11-mer peptides (Lundegaard et al. 2008)." . _:b430238899 "2"^^ . _:b430238491 "6"^^ . _:b430238917 . _:b430238808 . _:b430238671 . _:b430238898 "2"^^ . _:b430238488 "6"^^ . _:b430238916 . . . _:b7457989 "It has been suggested that supertype-specific differences exist in how dependent MHC class I presentation of peptides is on transport via TAP molecules (Brusic et al. 1999; Anderson et al. >>1993<<; Henderson et al. 1992; Smith and Lutz 1996) and proteasomal cleavage (Wherry et al. 2006)." . _:b430238909 "2"^^ . _:b430238489 "6"^^ . _:b430238919 . _:b430238469 . _:b430238688 . . _:b430238908 "2"^^ . _:b430238918 . . _:b430238787 . _:b430238442 . _:b430238911 "2"^^ . . _:b430238501 "5"^^ . . _:b430238913 . . _:b430238500 "5"^^ . _:b7457997 . _:b430238910 "2"^^ . _:b430238912 . _:b430238567 . _:b430238706 . _:b430238503 "5"^^ . _:b430238905 "2"^^ . . _:b430238915 . _:b430238502 "5"^^ . _:b430238904 "2"^^ . _:b430238914 . . . _:b430238497 "5"^^ . _:b430238907 "2"^^ . _:b430238925 . . _:b430238859 . _:b430238496 "5"^^ . _:b430238906 "2"^^ . _:b430238924 . _:b430238499 "5"^^ . _:b430238917 "2"^^ . _:b430238927 . . _:b430238498 "5"^^ . _:b7457995 . _:b430238916 "2"^^ . _:b430238926 . _:b430238509 "5"^^ . _:b430238919 "2"^^ . . _:b7458012 "Whether this observation reflects true biological aspects of the specificity overlap between the three pathway players (see for instance Nielsen et al. >>2005<<) or it simply occurs because the prediction of MHC class I affinity has gained accuracy during the recent years, whereas predictors for TAP transport efficiency and proteasomal cleavage have not changed or been updated, remains to be seen." . _:b430238921 . _:b7458006 "It has been evaluated as the best pan-specific method in large benchmark study (Zhang et al. 2009 and is now including the extension to perform predictions for 8-, 10-, and 11-mer peptides (Lundegaard et al. >>2008<<). NetMHCpan-2.2 was trained on a data set of 102,146 quantitative peptide\u2013MHC affinity data points covering more than 100 distinct MHC molecules. The prediction server is available at http://www.cbs.dtu.dk/services/NetMHCpan-2.2/." . _:b430238616 . _:b430238508 "5"^^ . _:b430238918 "2"^^ . _:b430238920 . _:b430238511 "5"^^ . _:b430238913 "2"^^ . _:b430238923 . _:b430238510 "5"^^ . _:b430238912 "2"^^ . . _:b430238525 . _:b430238922 . _:b430238505 "5"^^ . _:b430238915 "2"^^ . _:b430238504 "5"^^ . _:b430238914 "2"^^ . . _:b430238507 "5"^^ . _:b430238925 "2"^^ . _:b430238506 "5"^^ . _:b430238924 "2"^^ . _:b430238517 "4"^^ . _:b430238556 . _:b430238927 "2"^^ . . _:b430238825 . _:b430238516 "4"^^ . _:b430238926 "2"^^ . _:b430238723 . _:b430238519 "4"^^ . _:b430238921 "2"^^ . _:b7457970 . . _:b430238518 "4"^^ . _:b430238920 "2"^^ . . _:b430238796 . . _:b430238923 "2"^^ . _:b430238513 "5"^^ . _:b430238892 . _:b430238512 "5"^^ . _:b430238922 "2"^^ . _:b7457983 . . _:b430238515 "5"^^ . _:b430238845 . _:b430238518 . . _:b430238514 "5"^^ . _:b7457969 "These peptides may be trimmed at the N-terminal end by cytosolic exopeptidases (L\u00E9vy et al. >>2002<<). A subset of the peptides is transported by transporter associated with antigen processing (TAP) complex into the endoplasmatic reticulum (ER), where further N-terminal trimming occurs (Ritz and Seliger 2001; Koch et al. 2004; van Endert" . . _:b430238515 . _:b430238525 "4"^^ . _:b430238524 "4"^^ . _:b430238621 . _:b430238686 . _:b430238527 "4"^^ . _:b430238526 "4"^^ . . _:b430238802 . _:b430238521 "4"^^ . _:b7458013 . _:b430238765 . . . _:b430238520 "4"^^ . _:b430238523 "4"^^ . _:b430238766 . _:b430238522 "4"^^ . . . _:b430238533 "4"^^ . _:b7458001 . _:b7457973 . _:b430238563 . _:b430238532 "4"^^ . _:b430238884 . _:b430238885 . _:b430238886 . _:b430238887 . _:b430238535 "4"^^ . _:b430238880 . _:b430238881 . _:b430238882 . _:b430238883 . . _:b430238828 . _:b430238892 . _:b430238534 "4"^^ . . _:b430238893 . _:b430238894 . _:b430238895 . _:b430238479 . _:b430238888 . _:b430238529 "4"^^ . _:b430238889 . _:b430238890 . _:b430238891 . _:b430238528 "4"^^ . _:b430238900 . _:b430238901 . . _:b430238674 . _:b430238902 . _:b430238903 . _:b430238531 "4"^^ . _:b430238896 . _:b430238897 . _:b430238898 . _:b430238874 . . _:b430238899 . . . _:b430238908 . _:b430238530 "4"^^ . . _:b430238909 . _:b430238750 . _:b430238910 . _:b430238911 . _:b430238541 "4"^^ . _:b7457993 . _:b430238904 . _:b430238905 . _:b430238714 . . _:b430238906 . _:b430238907 . _:b430238540 "4"^^ . _:b430238852 . _:b430238853 . _:b430238854 . . _:b430238855 . _:b430238543 "4"^^ . _:b430238848 . _:b430238849 . _:b430238850 . _:b7457970 "A subset of the peptides is transported by transporter associated with antigen processing (TAP) complex into the endoplasmatic reticulum (ER), where further N-terminal trimming occurs (Ritz and Seliger >>2001<<; Koch et al. 2004; van Endert et al. 1994; Schatz et al. 2008)." . . _:b430238851 . _:b430238758 . _:b430238542 "4"^^ . _:b430238860 . _:b430238861 . _:b430238721 . "PMC0" . _:b430238862 . _:b430238863 . _:b430238715 . . _:b430238856 . _:b430238537 "4"^^ . _:b430238857 . _:b430238858 . _:b430238859 . _:b430238536 "4"^^ . _:b430238868 . . _:b430238869 . _:b430238870 . _:b430238603 . _:b430238871 . _:b430238539 "4"^^ . _:b430238864 . _:b430238865 . _:b430238866 . _:b430238867 . _:b430238538 "4"^^ . _:b430238876 . _:b430238877 . _:b430238878 . _:b430238815 . _:b430238879 . _:b430238489 . _:b430238872 . _:b430238549 "4"^^ . _:b430238873 . _:b430238874 . . _:b430238669 . _:b430238875 . _:b430238548 "4"^^ . _:b430238551 "4"^^ . . _:b430238550 "4"^^ . _:b430238902 . _:b7458021 "It consists of 216 HLA class I ligand pairs with corresponding source proteins covering the 12 supertypes (Lund et al. >>2004<<)." . _:b430238545 "4"^^ . _:b430238544 "4"^^ . . . _:b7457999 "These results clearly confirm earlier findings (P\u00E9rez et al. 2008; Hoof et al. >>2009<<) of the importance of going beyond HLA supertypes and the use of full-type HLA restriction information when identifying MHC class I epitopes." . _:b430238547 "4"^^ . _:b430238620 . _:b430238546 "4"^^ . . _:b430238577 . _:b430238557 "4"^^ . _:b430238916 . _:b430238556 "4"^^ . _:b430238917 . _:b430238918 . . . _:b430238919 . _:b430238912 . _:b430238559 "4"^^ . _:b430238913 . _:b430238891 . _:b430238914 . _:b430238915 . _:b7457969 . . _:b430238558 "4"^^ . _:b430238924 . _:b430238925 . _:b430238926 . _:b430238582 . _:b430238927 . . _:b7457981 . _:b430238920 . _:b430238553 "4"^^ . _:b430238921 . _:b430238900 . _:b430238469 . . _:b430238922 . _:b430238923 . _:b430238552 "4"^^ . _:b430238468 . _:b430238910 . _:b430238553 . _:b430238836 . _:b430238555 "4"^^ . _:b430238471 . . _:b430238554 "4"^^ . . _:b430238470 . _:b430238565 "4"^^ . _:b430238465 . . _:b430238756 . _:b430238564 "4"^^ . _:b430238757 . . _:b430238464 . _:b430238758 . _:b430238759 . _:b430238567 "3"^^ . _:b430238752 . . _:b430238664 . _:b430238753 . _:b430238467 . _:b430238754 . _:b430238755 . . _:b430238566 "4"^^ . _:b430238764 . _:b430238765 . _:b430238466 . _:b430238766 . _:b430238767 . _:b430238760 . _:b430238561 "4"^^ . . _:b430238761 . _:b430238477 . _:b430238762 . _:b430238763 . _:b430238772 . _:b430238560 "4"^^ . _:b430238773 . _:b7458014 "materials" . _:b430238774 . . _:b430238476 . _:b430238775 . . _:b430238768 . _:b430238563 "4"^^ . . _:b430238769 . _:b430238479 . _:b430238770 . _:b430238771 . _:b430238780 . _:b430238562 "4"^^ . . _:b430238781 . _:b430238478 . . _:b430238782 . _:b430238783 . _:b430238573 "3"^^ . _:b430238776 . . _:b430238777 . _:b430238473 . _:b430238778 . _:b430238779 . _:b430238572 "3"^^ . _:b430238724 . _:b430238725 . _:b430238472 . _:b430238726 . _:b430238727 . _:b430238697 . _:b430238575 "3"^^ . _:b430238720 . . _:b430238721 . _:b430238475 . _:b430238722 . _:b430238723 . _:b430238578 . _:b430238574 "3"^^ . _:b430238732 . _:b430238733 . _:b430238838 . _:b430238474 . _:b430238734 . _:b430238735 . _:b430238569 "3"^^ . _:b430238728 . _:b430238729 . _:b430238485 . _:b430238730 . . _:b430238568 "3"^^ . _:b430238731 . . _:b430238740 . _:b430238916 . _:b430238741 . . _:b430238484 . _:b430238742 . _:b430238743 . _:b430238571 "3"^^ . _:b430238506 . _:b430238736 . _:b430238737 . _:b430238604 . _:b430238487 . _:b430238738 . _:b430238739 . _:b430238570 "3"^^ . . _:b430238748 . _:b430238749 . _:b430238486 . _:b430238750 . _:b430238751 . _:b430238581 "3"^^ . _:b430238744 . _:b430238745 . _:b430238481 . _:b430238677 . _:b430238746 . . _:b430238747 . _:b430238832 . _:b430238580 "3"^^ . _:b430238820 . _:b430238821 . _:b7457998 "These results clearly confirm earlier findings (P\u00E9rez et al. >>2008<<; Hoof et al. 2009) of the importance of going beyond HLA supertypes and the use of full-type HLA restriction information when identifying MHC class I epitopes." . _:b430238480 . _:b430238822 . _:b430238823 . _:b430238583 "3"^^ . _:b430238816 . _:b7458023 . _:b430238817 . _:b430238483 . . _:b430238818 . _:b430238819 . _:b430238582 "3"^^ . _:b430238828 . _:b430238829 . _:b430238482 . _:b430238830 . . _:b430238577 "3"^^ . _:b430238831 . _:b430238824 . _:b430238840 . _:b430238760 . _:b430238825 . _:b430238495 . . _:b430238826 . _:b430238493 . _:b430238827 . _:b430238576 "3"^^ . _:b430238836 . _:b430238837 . _:b430238665 . _:b430238492 . _:b430238838 . _:b430238839 . _:b430238579 "3"^^ . _:b430238832 . _:b430238833 . _:b430238495 . _:b430238641 . _:b430238834 . _:b430238835 . _:b430238578 "3"^^ . _:b430238844 . _:b430238845 . _:b430238494 . _:b430238846 . . _:b430238589 "3"^^ . _:b430238847 . . _:b430238840 . _:b430238841 . _:b430238489 . _:b430238823 . _:b430238842 . _:b430238843 . _:b430238588 "3"^^ . _:b430238788 . _:b430238789 . _:b430238488 . _:b430238790 . _:b430238791 . _:b430238591 "3"^^ . _:b430238784 . _:b430238785 . _:b430238491 . _:b430238626 . _:b430238786 . _:b430238787 . _:b430238590 "3"^^ . _:b430238796 . . _:b430238797 . _:b430238490 . _:b430238798 . _:b430238799 . _:b430238585 "3"^^ . . _:b430238792 . _:b430238793 . _:b430238501 . _:b430238794 . _:b430238795 . _:b430238584 "3"^^ . _:b430238804 . . _:b430238805 . _:b430238500 . _:b430238806 . _:b430238807 . _:b430238609 . _:b430238587 "3"^^ . _:b430238800 . . _:b7457965 "in MHC class I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al. 1997; Altuvia and Margalit >>2000<<; Mo et al. 1999; Stoltze et al. 1998; Juncker et al. 2009). These peptides may be trimmed at the N-terminal end by cytosolic exopeptidases (L\u00E9vy et al. 2002)." . _:b430238679 . _:b430238801 . _:b430238503 . _:b430238802 . . _:b430238586 "3"^^ . _:b430238803 . . _:b430238812 . _:b430238813 . _:b430238502 . _:b430238814 . . _:b430238597 "3"^^ . _:b430238815 . _:b430238808 . _:b430238809 . _:b430238497 . _:b7457962 "One of the first steps involved in MHC class I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. >>2007<<; Paz et al. 1999; Craiu et al. 1997; Altuvia and Margalit 2000; Mo et al. 1999; Stoltze et al. 1998; Juncker et al. 2009)." . _:b430238810 . _:b430238811 . _:b430238596 "3"^^ . _:b430238628 . . _:b430238629 . _:b430238496 . _:b430238630 . . _:b430238631 . _:b430238627 . _:b430238599 "3"^^ . . _:b430238624 . _:b430238653 . _:b430238625 . _:b430238499 . _:b430238626 . _:b430238627 . _:b430238598 "3"^^ . _:b430238490 . _:b430238636 . . _:b7457977 . _:b430238637 . _:b430238498 . _:b430238638 . . _:b430238593 "3"^^ . _:b430238639 . _:b430238538 . _:b430238632 . _:b430238633 . . _:b430238509 . _:b430238634 . . _:b430238773 . _:b430238592 "3"^^ . _:b430238635 . . _:b430238644 . _:b430238645 . _:b430238508 . _:b430238646 . _:b430238647 . _:b430238713 . _:b430238595 "3"^^ . _:b430238542 . _:b430238640 . . _:b430238707 . _:b430238658 . _:b430238641 . _:b430238511 . _:b430238642 . . _:b430238594 "3"^^ . _:b430238643 . . _:b430238652 . . _:b430238653 . _:b430238510 . _:b430238654 . _:b430238454 . _:b430238605 "3"^^ . _:b430238655 . _:b430238648 . . _:b430238657 . _:b430238649 . _:b430238505 . _:b430238650 . _:b430238651 . _:b430238604 "3"^^ . _:b430238596 . _:b430238597 . _:b430238747 . _:b430238504 . _:b430238598 . . . . _:b430238599 . _:b7458017 . _:b430238607 "3"^^ . _:b430238592 . _:b430238593 . _:b430238507 . _:b430238594 . _:b430238595 . _:b430238606 "3"^^ . _:b430238604 . . . _:b430238605 . . _:b430238506 . . _:b430238606 . _:b430238607 . _:b430238601 "3"^^ . _:b430238600 . _:b430238858 . _:b430238601 . _:b7457994 "Likewise, it has been suggested that the rescaling procedure commonly used to correct for possible discrepancies between the allelic predictors (Sturniolo et al. 1999; Larsen et al. 2005, >>2007<<) could mask genuine biological difference between MHC molecules and potentially lower the epitope predictive performance (MacNamara et al. 2009)." . _:b430238517 . _:b430238602 . _:b430238603 . _:b430238600 "3"^^ . _:b430238612 . _:b430238613 . _:b430238516 . _:b430238614 . _:b430238615 . _:b430238603 "3"^^ . _:b430238608 . _:b430238609 . _:b430238476 . . _:b430238610 . _:b430238519 . _:b430238611 . _:b430238602 "3"^^ . _:b7458002 "methods" . _:b430238620 . . _:b430238621 . . _:b430238518 . _:b430238622 . . _:b430238623 . _:b430238613 "3"^^ . _:b430238616 . . . _:b430238617 . . _:b430238513 . _:b430238618 . _:b430238619 . _:b430238612 "3"^^ . _:b430238692 . _:b430238693 . _:b430238512 . _:b430238694 . _:b430238695 . _:b430238615 "3"^^ . _:b430238688 . _:b430238689 . _:b430238515 . _:b430238639 . _:b430238690 . _:b430238691 . _:b430238614 "3"^^ . _:b430238700 . _:b430238701 . _:b430238514 . _:b430238702 . _:b430238703 . _:b430238609 "3"^^ . _:b430238696 . _:b430238697 . _:b430238525 . _:b430238698 . . _:b430238608 "3"^^ . _:b430238699 . . _:b430238708 . _:b430238709 . _:b430238524 . _:b430238794 . _:b430238710 . _:b430238711 . _:b430238611 "3"^^ . _:b430238704 . _:b430238705 . _:b430238527 . _:b430238706 . _:b430238707 . _:b430238610 "3"^^ . _:b430238716 . . _:b430238717 . _:b430238526 . _:b430238718 . _:b430238719 . _:b430238621 "3"^^ . _:b430238712 . _:b430238681 . _:b430238713 . _:b430238927 . _:b430238521 . _:b430238714 . . _:b430238447 . _:b430238620 "3"^^ . _:b430238715 . _:b430238660 . _:b430238661 . _:b430238520 . _:b430238662 . _:b430238663 . _:b430238623 "3"^^ . _:b430238656 . _:b430238839 . . _:b430238657 . _:b430238523 . _:b430238658 . . _:b7457971 "A subset of the peptides is transported by transporter associated with antigen processing (TAP) complex into the endoplasmatic reticulum (ER), where further N-terminal trimming occurs (Ritz and Seliger 2001; Koch et al. >>2004<<; van Endert et al. 1994; Schatz et al. 2008)." . _:b430238622 "3"^^ . _:b430238659 . _:b430238668 . _:b430238672 . _:b430238669 . _:b430238741 . _:b430238540 . _:b430238670 . _:b430238522 . _:b430238671 . _:b7458003 . _:b430238617 "3"^^ . _:b430238664 . _:b430238665 . _:b430238533 . _:b430238666 . _:b430238667 . _:b430238926 . _:b430238616 "3"^^ . _:b430238676 . _:b430238677 . _:b430238532 . _:b430238678 . _:b430238679 . _:b430238924 . _:b430238619 "3"^^ . _:b430238596 . _:b430238672 . _:b7458019 "Data used for training the individual MHC class I pathway predictors\u2014MHC binding (Nielsen et al. 2007; Hoof et al. 2009), proteasomal cleavage (Nielsen et al. 2005), and TAP transport efficiency (Peters et al. >>2003<<)\u2014was removed from the data set, downsizing it to 2,309 unique HLA class I ligand pairs." . _:b430238673 . _:b7458013 "In order to easily grasp the predictive performance gain, we applied the rank measure as defined by Larsen et al. (>>2005<<). The rank measure reports the average fraction of epitopes identified as a function of the percentage rank (percentage of tested peptides) for a set of proteins. This measure indicates how large a fraction of the peptides for a given" . . _:b430238674 . _:b430238493 . _:b430238535 . . _:b7458012 . _:b430238618 "3"^^ . _:b430238675 . _:b430238684 . _:b430238668 . _:b430238685 . _:b430238534 . _:b430238777 . _:b430238686 . _:b430238687 . _:b430238629 "3"^^ . _:b430238680 . _:b430238681 . _:b430238682 . . _:b430238529 . _:b430238683 . _:b7458000 . _:b430238628 "3"^^ . _:b430238500 . _:b430238501 . _:b430238502 . _:b430238528 . _:b430238503 . _:b430238631 "3"^^ . _:b430238496 . _:b430238680 . _:b430238497 . _:b430238753 . _:b430238498 . _:b430238531 . _:b430238499 . _:b7457995 "discrepancies between the allelic predictors (Sturniolo et al. 1999; Larsen et al. 2005, 2007) could mask genuine biological difference between MHC molecules and potentially lower the epitope predictive performance (MacNamara et al. >>2009<<). In the context of the NetCTLpan method, we investigate to what extend such differences are observed in large data sets that are diverse with regard to both MHC restriction and CTL epitopes." . _:b430238630 "3"^^ . . _:b430238508 . _:b430238879 . _:b430238509 . _:b430238689 . . _:b430238510 . _:b430238530 . _:b430238511 . _:b7458009 . _:b430238625 "3"^^ . _:b430238504 . _:b430238505 . _:b430238506 . _:b430238541 . _:b430238507 . _:b430238647 . _:b430238624 "3"^^ . _:b430238516 . _:b430238517 . _:b430238518 . _:b430238540 . _:b430238519 . _:b430238627 "3"^^ . _:b430238512 . _:b430238870 . _:b430238513 . _:b430238514 . _:b7458024 "In these cases, the association was assigned by applying the classification from the work by Sidney et al. (>>2008<<). The associated supertypes for each HLA class I allele are shown in Supplementary Table\u00A0S1. Some supertypes in the 9-mer SYF data set contain more HLA class I ligand pairs than others. Only four out of the 12 supertypes had more than 100" . . _:b430238543 . _:b430238515 . _:b430238626 "3"^^ . _:b430238524 . . . _:b430238525 . _:b430238526 . _:b430238542 . _:b430238527 . _:b7457999 . _:b430238637 "3"^^ . _:b430238520 . _:b430238521 . _:b430238522 . _:b430238890 . _:b430238537 . . _:b430238523 . _:b7458018 . _:b430238636 "3"^^ . . _:b430238468 . _:b430238469 . _:b430238618 . _:b430238470 . _:b430238536 . _:b430238471 . _:b430238639 "3"^^ . _:b430238464 . _:b430238465 . _:b430238466 . _:b430238539 . _:b430238467 . _:b430238638 "3"^^ . _:b430238476 . . _:b430238477 . _:b430238478 . _:b430238538 . _:b430238479 . _:b430238633 "3"^^ . _:b430238472 . _:b430238894 . _:b430238855 . . _:b430238473 . _:b430238474 . _:b430238549 . _:b430238475 . _:b430238632 "3"^^ . _:b430238484 . _:b430238660 . . _:b430238485 . _:b430238486 . _:b430238548 . _:b430238487 . _:b430238635 "3"^^ . _:b430238480 . . _:b430238481 . . _:b430238482 . _:b430238551 . _:b430238483 . _:b7457978 "The NetCTL method has proven successful in identification of CTL epitopes from, for instance influenza (Wang et al. 2007), HIV (P\u00E9rez et al. >>2008<<), and Orthopoxvirus (Tang et al. 2008)." . _:b430238634 "3"^^ . . _:b430238492 . _:b430238594 . _:b430238493 . _:b430238637 . _:b430238494 . _:b430238550 . _:b430238495 . _:b430238645 "3"^^ . . _:b430238488 . _:b430238683 . _:b430238489 . _:b430238490 . _:b430238545 . _:b430238491 . _:b430238816 . _:b430238644 "3"^^ . _:b430238564 . _:b430238565 . _:b430238566 . _:b430238544 . _:b430238567 . _:b430238647 "3"^^ . . _:b430238560 . _:b430238886 . _:b430238561 . _:b430238562 . _:b430238547 . _:b430238563 . _:b430238646 "3"^^ . _:b430238572 . _:b430238512 . . _:b430238573 . . _:b7457971 . _:b430238546 . _:b430238574 . _:b430238575 . _:b430238641 "3"^^ . . . _:b430238568 . _:b430238569 . _:b7458023 "supertype defined in terms of the correlation coefficient between NetMHCpan prediction scores for 1,000,000 random natural 9-mer peptides for the HLA allele in question and any of the 12 supertype representatives (Larsen et al. >>2005<<). In a few cases (less than ten), the supertype association was ambiguous. In these cases, the association was assigned by applying the classification from the work by Sidney et al. (2008)." . . _:b430238557 . _:b430238570 . _:b430238571 . _:b430238640 "3"^^ . _:b430238580 . _:b7458004 "The current version of the pan-specific MHC class I binding prediction method, NetMHCpan-2.2 (Hoof et al. 2009), is an updated version of the original NetMHCpan method (Nielsen et al. >>2007<<). It has been evaluated as the best pan-specific method in large benchmark study (Zhang et al. 2009 and is now including the extension to perform predictions for 8-, 10-, and 11-mer peptides (Lundegaard et al. 2008)." . _:b430238581 . _:b430238582 . _:b430238556 . . _:b430238583 . _:b430238643 "3"^^ . _:b430238576 . _:b430238577 . _:b430238578 . _:b430238559 . . _:b430238642 "3"^^ . _:b430238579 . _:b430238588 . _:b430238788 . _:b430238589 . _:b430238590 . _:b430238558 . _:b430238591 . _:b430238653 "3"^^ . _:b430238584 . _:b430238446 . _:b430238585 . _:b430238579 . _:b430238586 . _:b430238553 . _:b430238587 . _:b430238652 "3"^^ . . _:b430238532 . _:b430238533 . _:b430238779 . _:b430238534 . _:b430238552 . _:b430238535 . _:b430238871 . _:b430238655 "3"^^ . . _:b430238528 . . _:b430238529 . _:b430238530 . _:b430238555 . _:b430238531 . _:b430238654 "3"^^ . _:b430238540 . _:b430238541 . _:b430238542 . _:b7457963 . _:b430238554 . _:b430238543 . _:b430238649 "3"^^ . _:b430238536 . _:b7457980 . _:b430238537 . _:b430238752 . _:b430238538 . _:b430238565 . _:b430238539 . _:b7458005 . _:b7457988 "It has been suggested that supertype-specific differences exist in how dependent MHC class I presentation of peptides is on transport via TAP molecules (Brusic et al. >>1999<<; Anderson et al. 1993; Henderson et al. 1992; Smith and Lutz 1996) and proteasomal cleavage (Wherry et al. 2006)." . _:b430238748 . _:b430238648 "3"^^ . _:b430238548 . . _:b430238549 . _:b430238850 . . _:b430238550 . _:b430238564 . _:b430238551 . _:b430238651 "3"^^ . . _:b430238544 . _:b430238545 . _:b430238546 . _:b430238567 . _:b430238547 . _:b430238810 . _:b430238650 "3"^^ . _:b430238451 . _:b430238556 . _:b430238557 . . _:b430238558 . _:b430238661 "2"^^ . _:b430238566 . _:b430238559 . . _:b430238552 . _:b430238507 . . . _:b430238553 . . _:b430238660 "2"^^ . _:b430238561 . _:b430238554 . _:b430238555 . _:b430238560 . _:b430238875 . _:b430238663 "2"^^ . . _:b430238563 . _:b430238662 "2"^^ . . . . _:b430238562 . _:b430238657 "3"^^ . _:b430238573 . _:b430238656 "3"^^ . . . _:b430238463 . _:b430238572 . _:b430238659 "2"^^ . _:b430238725 . _:b430238575 . _:b430238658 "3"^^ . _:b430238574 . _:b430238669 "2"^^ . . _:b430238569 . _:b430238668 "2"^^ . _:b430238729 . _:b430238555 . _:b430238568 . _:b430238671 "2"^^ . _:b430238552 . _:b430238571 . _:b430238670 "2"^^ . _:b430238570 . _:b7457966 . _:b430238665 "2"^^ . . . _:b430238664 "2"^^ . _:b430238581 . _:b430238580 . _:b430238704 . _:b430238667 "2"^^ . _:b430238583 . _:b430238666 "2"^^ . . _:b430238582 . _:b430238677 "2"^^ . . _:b430238755 . . _:b430238857 . _:b430238649 . _:b430238577 . _:b430238676 "2"^^ . _:b430238576 . _:b7458006 . _:b430238679 "2"^^ . _:b430238851 . . _:b430238865 . _:b430238579 . _:b430238678 "2"^^ . _:b430238804 . _:b430238444 . _:b430238445 . _:b430238446 . _:b430238673 "2"^^ . _:b430238578 . . _:b430238447 . . _:b430238442 . _:b430238672 "2"^^ . _:b430238589 . _:b430238443 . . _:b430238452 . _:b430238453 . _:b430238454 . _:b430238675 "2"^^ . _:b430238588 . _:b430238455 . _:b430238448 . _:b430238449 . _:b430238503 . _:b430238450 . _:b430238674 "2"^^ . _:b430238591 . _:b430238451 . _:b7457975 "We have previously described a method, NetCTL (Larsen et al. >>2007<<, 2005), integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions to an overall prediction of CTL epitopes." . _:b430238443 . _:b430238460 . _:b430238461 . _:b430238462 . _:b430238685 "2"^^ . _:b430238590 . _:b430238463 . _:b430238456 . _:b430238457 . _:b430238458 . _:b430238684 "2"^^ . _:b430238585 . _:b430238459 . _:b430238584 . _:b430238687 "2"^^ . _:b7458016 "Data used for training the individual MHC class I pathway predictors\u2014MHC binding (Nielsen et al. >>2007<<; Hoof et al. 2009), proteasomal cleavage (Nielsen et al. 2005), and TAP transport efficiency (Peters et al. 2003)\u2014was removed from the data set, downsizing it to 2,309 unique HLA class I ligand pairs." . _:b430238732 . _:b430238712 . . _:b430238686 "2"^^ . _:b430238587 . . . _:b430238586 . _:b430238681 "2"^^ . _:b430238690 . _:b430238597 . _:b430238680 "2"^^ . . _:b430238596 . _:b430238691 . _:b430238683 "2"^^ . _:b430238599 . _:b430238682 "2"^^ . _:b430238598 . _:b430238693 "2"^^ . _:b430238611 . . _:b7458020 "The same HIV data set has been used as for the paper describing the original NetCTL method (Larsen et al. >>2007<<). For comparison reasons, the data set has not been updated. The data set is derived from the Los Alamos HIV database (http:" . _:b430238593 . _:b7457968 "of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al. 1997; Altuvia and Margalit 2000; Mo et al. 1999; Stoltze et al. 1998; Juncker et al. >>2009<<). These peptides may be trimmed at the N-terminal end by cytosolic exopeptidases (L\u00E9vy et al. 2002)." . _:b430238692 "2"^^ . . _:b430238592 . _:b430238695 "2"^^ . _:b430238675 . _:b430238595 . _:b430238717 . _:b430238694 "2"^^ . _:b7457964 . _:b430238594 . _:b430238689 "2"^^ . _:b430238484 . _:b7457984 "In a large-scale benchmark evaluation of publicly available server of MHC class I pathway presentation prediction, Larsen et al. (>>2007<<) showed that the NetCTL method significantly outperformed all these methods, closely followed by MHC-pathway." . _:b430238605 . _:b430238688 "2"^^ . _:b430238604 . _:b7457993 "Likewise, it has been suggested that the rescaling procedure commonly used to correct for possible discrepancies between the allelic predictors (Sturniolo et al. 1999; Larsen et al. >>2005<<, 2007) could mask genuine biological difference between MHC molecules and potentially lower the epitope predictive performance (MacNamara et al. 2009)." . _:b430238691 "2"^^ . _:b430238607 . _:b430238690 "2"^^ . _:b430238629 . _:b430238606 . _:b430238701 "2"^^ . . _:b430238600 . . _:b430238700 "2"^^ . _:b430238601 . _:b430238520 . _:b430238600 . _:b430238703 "2"^^ . . _:b430238780 . . _:b430238488 . . . _:b430238774 . _:b430238702 "2"^^ . _:b430238603 . _:b430238584 . _:b430238466 . _:b430238697 "2"^^ . _:b430238602 . . . _:b430238613 . _:b430238696 "2"^^ . _:b430238790 . _:b430238612 . _:b430238699 "2"^^ . . _:b430238445 . _:b430238698 "2"^^ . _:b430238615 . . _:b430238614 . _:b430238709 "2"^^ . . . _:b430238708 "2"^^ . _:b430238642 . _:b430238609 . _:b430238608 . _:b430238711 "2"^^ . . _:b430238499 . _:b430238611 . _:b430238710 "2"^^ . . _:b430238705 "2"^^ . _:b430238610 . _:b430238621 . _:b430238704 "2"^^ . . . _:b430238620 . _:b430238707 "2"^^ . _:b7457982 . _:b430238623 . _:b430238706 "2"^^ . _:b430238535 . . _:b430238717 "2"^^ . _:b430238684 . _:b430238622 . _:b430238562 . _:b430238761 . _:b430238617 . _:b430238868 . _:b430238716 "2"^^ . . _:b430238887 . _:b430238655 . . _:b430238719 "2"^^ . _:b430238616 . _:b430238459 . _:b430238733 . _:b430238718 "2"^^ . _:b430238619 . . . _:b430238713 "2"^^ . _:b430238618 . _:b430238863 . _:b430238629 . _:b430238712 "2"^^ . _:b430238591 . _:b430238628 . _:b430238715 "2"^^ . _:b430238827 . _:b430238888 . _:b430238487 . _:b430238714 "2"^^ . _:b430238631 . _:b430238630 . _:b7457966 "I antigen presentation is the degradation of intracellular proteins, including proteins from the cytoplasm and nucleus, by the proteasome (Larsen et al. 2007; Paz et al. 1999; Craiu et al. 1997; Altuvia and Margalit 2000; Mo et al. >>1999<<; Stoltze et al. 1998; Juncker et al. 2009). These peptides may be trimmed at the N-terminal end by cytosolic exopeptidases (L\u00E9vy et al. 2002)." . _:b430238532 . _:b430238560 . _:b430238460 . _:b430238625 . _:b430238588 . _:b430238628 . _:b430238650 . _:b430238624 . . . _:b430238627 . . . _:b430238626 . _:b430238472 . . _:b430238539 . _:b430238637 . _:b430238572 . _:b430238636 . _:b430238444 . _:b430238571 . _:b430238639 . _:b430238833 . _:b430238638 . _:b7458004 . _:b430238640 . _:b430238470 . . _:b430238633 . . _:b430238632 . . _:b430238739 . _:b430238544 . _:b430238789 . _:b430238635 . . _:b430238685 . . _:b430238516 . _:b430238634 . _:b430238462 . . . _:b430238645 . _:b430238737 . _:b430238644 . _:b430238647 . _:b430238646 . _:b430238636 . _:b430238646 . . _:b430238449 . _:b430238641 . . _:b430238640 . _:b430238740 . _:b430238898 . _:b430238643 . _:b430238565 . _:b430238642 . _:b7457992 "Likewise, it has been suggested that the rescaling procedure commonly used to correct for possible discrepancies between the allelic predictors (Sturniolo et al. >>1999<<; Larsen et al. 2005, 2007) could mask genuine biological difference between MHC molecules and potentially lower the epitope predictive performance (MacNamara et al. 2009)." . _:b430238605 . _:b430238653 . _:b430238652 . _:b430238564 . _:b7458021 . _:b430238655 . _:b7457967 . . _:b430238654 . _:b430238754 . . _:b430238649 . _:b430238772 . _:b430238648 . . _:b430238651 . . _:b430238771 . _:b430238650 . . _:b430238661 . . _:b430238660 . _:b7457998 . . _:b430238883 . _:b430238663 . _:b430238659 . _:b430238860 . _:b430238662 . _:b430238882 . . _:b430238657 . . _:b430238656 . _:b430238593 . _:b7457975 . _:b430238659 . . . _:b430238769 . _:b430238658 . . _:b430238698 . _:b430238728 . . . . _:b430238669 . _:b7457962 . . _:b430238668 . . _:b430238671 . _:b430238848 . . _:b430238510 . . _:b430238670 . . _:b430238665 . . _:b430238701 . _:b430238812 .